Smoke and Mirrors – and Red Tape

Smoke and Mirrors – and Red Tape

Knowledge lags behind practice on medical marijuana. Cutting back on excessive bureaucracy for researchers is likely to help us all catch up.

In August 2016, the US Drug Enforcement Agency (DEA) lifted rules that restricted scientists to a single, government-run source of marijuana for medical research. For the past four decades, all cannabis for research in the US has come from a tightly controlled growing facility at the University of Mississippi. With medical marijuana legalized in 25 US states, the DEA accepts that an expanded supply and greater variety of marijuana for research is needed.

However, cannabis remains a Schedule I substance in the US, and researchers wishing to study the drug have a number of regulatory hoops to jump through, as well as tight controls on storage and handling. The knock-on effect is that funders and review boards are very wary of research involving marijuana, creating a somewhat contradictory situation – patients can access marijuana in many states, while medical researchers wishing to carry out clinical trials cannot. The drug remains Schedule I in part because there is a lack of evidence to justify medical use, but classification makes it an uphill slog for researchers to generate such evidence – classic catch-22. New pharmaceuticals can only be prescribed after extensive clinical trials have proven them to be safe and effective, but marijuana researchers are often restricted to small, open-label studies by funding and approval issues.

Despite the hurdles, there is evidence to suggest that cannabis and its active ingredients are effective in a number of therapeutic areas. The two FDA-approved cannabinoid drugs (Marinol and Syndros) are man-made versions of one of the main psychoactive ingredients of marijuana – tetrahydrocannabinol (THC) – and primarily used to stimulate appetite in AIDs or cancer patients (1, 2). Sativex, approved in Canada, New Zealand and several European countries to treat multiple-sclerosis-related spasticity, is directly derived from the cannabis plant, and contains mainly THC and non-psychoactive cannabidiol (CBD) (3). The addition of CBD is thought to mitigate the “high” and other side effects of THC, as well as enhancing efficacy of the drug. CBD is also showing promise in some hard-to-treat epilepsies (4).

However, by far the most common reason patients request a medical marijuana prescription is pain relief. And new painkillers are desperately needed for chronic pain; with more than 650,000 prescriptions for opioids dispensed daily in the US alone – and nonmedical use exploding – an ever-increasing number of people are becoming addicted, with tragic results. Seventy-nine Americans die every day as a result of opioid overdose (5), and opioid abuse is a problem worldwide. Like cannabinoids, opioids are derived from a plant, and have a long history of medical and recreational use.

Cannabis is not a replacement for opioids, which have unbeatable efficacy for acute pain and many types of cancer pain, but it is thought to be effective mainly for neuropathic pain, which is notoriously hard to control with existing therapies. Any therapy that can cut opioid prescriptions merits serious consideration, particularly one with a solid safety profile; the chances of dying from a marijuana overdose are vanishingly small. A JAMA meta-analysis concluded that there was moderate evidence to support the use of medical marijuana to treat pain (6), while pain patients receiving medical marijuana have reported that they were able to reduce or stop opioid painkillers (7). Researchers want to find out whether better pain control could account for the finding that states legalizing medical use of marijuana had an average of 25 percent fewer deaths from opioid overdose (8). However, that research is being held back by the polarized nature of the debate.

Though some of those in favor of legalization like to present the drug as a 100-percent-safe ‘cure all,’ cannabis – as with all drugs – is not without side effects (9, 10), which makes it all the more important that unbiased, controlled studies are conducted. Only rigorous research can clarify the benefit and harm of medical marijuana – and allow doctors, patients and governments to make informed decisions.

References

1. Abbvie, “Marinol”, Available at: www.marinol.com, (2016). Accessed September 7, 2016.
2. Insys Therapeutics, “Insys therapeutics announces fda approval of Syndros™”, (2016) Available at: www.syndros.com. Accessed September 7, 2016.
3. GW Pharmaceuticals, “Sativex”, (2016) Available at: www.gwpharm.com/sativex.aspx. Accessed September 7, 2016.
4. O Davinsky et al., “Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial”, Lancet Neurol, 15, 270–278 (2016). PMID: 26724101.
5. U.S. Department of Health and Human Services, “The opioid epidemic: by the numbers”, (2015) Available at: bit.ly/29zUJdz. Accessed September 7, 2016.
6. PF Whiting et al., “Cannabinoids for medical use: a systematic review and meta-analysis”, JAMA, 313, 2456–2473 (2015). PMID: 26103030.
7. S Haroutounian et al., “The effect of medicinal cannabis on pain and quality of life outcomes in chronic pain: a prospective open-label study”, Clin J Pain, [Epub ahead of print] (2016). PMID: 26889611.
8. MA Bachhuber et al.,“Medical cannabis laws and opioid analgesic overdose mortality in the united states, 1999-2010”, JAMA Intern Med, 174, 1668–1673 (2014). PMID: 25154332.
9. M Large et al., “Cannabis use and earlier onset of psychosis: a systematic meta-analysis”, Arch Gen Psychiatry, 68, 555–561 (2011). PMID: 21300939.
10. T Rubino, et al. “Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood”, Hippocampus 19, 763–772 (2009). PMID: 19156848.